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Threshold Effects in the Relationship Between Serum Non-High-Density Lipoprotein Cholesterol and Metabolic Syndrome.

ABSTRACT: Background:Previous studies have suggested that the non-high-density lipoprotein cholesterol (non-HDL-C) is strongly associated with metabolic syndrome (MetS); however, the explicit relationship between them has not yet been clarified. The aim of this study was to reveal the explicit association between the non-HDL-C with MetS. Methods:The present study was based on a cross-sectional study, which was carried out in Spain. A total of 60,799 workers were recruited between 2012 and 2016. Anthropometric parameters and blood indices (lipid profile and fasting blood glucose) were collected. Participants were divided into the MetS group or the non-MetS group based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III. The relationship between serum non-HDL-C and the risk of MetS was evaluated using multivariate regression analysis, piece-wise linear regression analysis, smooth curve fitting and threshold saturation effect analysis after adjustment of potential confounders. Results:The risk of developing MetS increased with increasing non-HDL-C level. However, this association was only presented in the range of the non-HDL-C concentrations from 118 mg/dl to 247 mg/dl after adjusting for potential confounders. When compared to lower non-HDL-C level (<118 mg/dl), higher levels of non-HDL-C (118-247 mg/dl and >247 mg/dl) were related to higher incidence of MetS, with adjusted odds ratio (95% confidence interval) of 3.08 (2.77, 3.42) and 17.18 (14.29, 20.65), respectively (P for trend <0.05). Conclusion:Higher serum non-HDL-C level was associated with increased MetS incidence; however, significant threshold saturation effects were observed when the non-HDL-C level <118 mg/dl or >247 mg/dl.

SUBMITTER: Wang S

PROVIDER: S-EPMC6890221 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Threshold Effects in the Relationship Between Serum Non-High-Density Lipoprotein Cholesterol and Metabolic Syndrome.

Wang Saibin S Tu Junwei J Pan Yibin Y

Diabetes, metabolic syndrome and obesity : targets and therapy 20191129

<h4>Background</h4>Previous studies have suggested that the non-high-density lipoprotein cholesterol (non-HDL-C) is strongly associated with metabolic syndrome (MetS); however, the explicit relationship between them has not yet been clarified. The aim of this study was to reveal the explicit association between the non-HDL-C with MetS.<h4>Methods</h4>The present study was based on a cross-sectional study, which was carried out in Spain. A total of 60,799 workers were recruited between 2012 and 2 ...[more]

PMID: 31819575

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Project description:BackgroundThere is accumulating evidence that serum levels of non-high-density lipoprotein cholesterol (non-HDL-C) are a more accurate predictor of cardiovascular outcomes when compared with low-density lipoprotein cholesterol. However, we recently found that higher serum concentrations of triglycerides are associated with better outcomes in patients undergoing hemodialysis. Therefore, we hypothesized that the association of serum levels of non-HDL-C (which includes triglyceride-rich lipoproteins) with outcomes may also be different in patients undergoing hemodialysis when compared with other patient populations.Methods and resultsWe studied the association of baseline and time-dependent serum levels of non-HDL-C with all-cause and cardiovascular mortality using Cox proportional hazard regression models in a nationally representative cohort of 50 118 patients undergoing incident hemodialysis from January 1, 2007, to December 31, 2011. In time-dependent models adjusted for case mix and surrogates of malnutrition and inflammation, a graded inverse association between non-HDL-C level and mortality was demonstrated with hazard ratios (95% confidence intervals) of the lowest (<60 mg/dL) and highest (?160 mg/dL) categories: 1.88 (1.72-2.06) and 0.73 (0.64-0.83) for all-cause mortality and 2.07 (1.78-2.41) and 0.75 (0.60-0.93) for cardiovascular mortality, respectively (reference, 100-115 mg/dL). In analyses using baseline values, non-HDL-C levels <100 mg/dL were also associated with significantly higher mortality risk across all levels of adjustment. Similar associations were found when evaluating non-HDL/HDL cholesterol ratio and mortality, with the highest all-cause and cardiovascular mortality being observed in patients with decreased non-HDL/HDL-C ratio (<2.5).ConclusionsContrary to the general population, decrements in non-HDL-C and non-HDL/HDL cholesterol ratio were paradoxically associated with increased all-cause and cardiovascular mortality in patients undergoing incident hemodialysis. The underlying mechanisms responsible for these associations await further investigation.

Project description:Adipose harbors a large depot of free cholesterol. However, a role for adipose in cholesterol lipidation of high-density lipoprotein (HDL) in vivo is not established. We present the first evidence that adipocytes support transfer of cholesterol to HDL in vivo as well as in vitro and implicate ATP-binding cassette subfamily A member 1 (ABCA1) and scavenger receptor class B type I (SR-BI), but not ATP-binding cassette subfamily G member 1 (ABCG1), cholesterol transporters in this process.Cholesterol efflux from wild-type, ABCA1(-/-), SR-BI(-/-), and ABCG1(-/-) adipocytes to apolipoprotein A-I (apoA-I) and HDL3 were measured in vitro. 3T3L1 adipocytes, labeled with (3)H-cholesterol, were injected intraperitoneally into wild-type, apoA-I transgenic, and apoA-I(-/-) mice, and tracer movement onto plasma HDL was monitored. Identical studies were performed with labeled wild-type, ABCA1(-/-), or SR-BI(-/-) mouse embryonic fibroblast adipocytes. The effect of tumor necrosis factor-alpha on transporter expression and cholesterol efflux was monitored during adipocyte differentiation. Cholesterol efflux to apoA-I and HDL3 was impaired in ABCA1(-/-) and SR-BI(-/-) adipocytes, respectively, with no effect observed in ABCG1(-/-) adipocytes. Intraperitoneal injection of labeled 3T3L1 adipocytes resulted in increased HDL-associated (3)H-cholesterol in apoA-I transgenic mice but reduced levels in apoA-I(-/-) animals. Intraperitoneal injection of labeled ABCA1(-/-) or SR-BI(-/-) adipocytes reduced plasma counts relative to their respective controls. Tumor necrosis factor-alpha reduced both ABCA1 and SR-BI expression and impaired cholesterol efflux from partially differentiated adipocytes.These data suggest a novel metabolic function of adipocytes in promoting cholesterol transfer to HDL in vivo and implicate adipocyte SR-BI and ABCA1, but not ABCG1, in this process. Furthermore, adipocyte modulation of HDL may be impaired in adipose inflammatory disease states such as type 2 diabetes mellitus.

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Threshold Effects in the Relationship Between Serum Non-High-Density Lipoprotein Cholesterol and Metabolic Syndrome.

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Threshold Effects in the Relationship Between Serum Non-High-Density Lipoprotein Cholesterol and Metabolic Syndrome.

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